Nexobrid 5 g powder and gel for gel

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

NexoBrid 5 g powder and gel for gel

concentrated proteolytic enzymes enriched with bromelain

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor.
• If you or your child experience any adverse effects, consult your doctor, even if they are effects not listed in this leaflet. See section 4.

Contents of the leaflet

1. What NexoBrid is and what it is used for
2. What you need to know before using NexoBrid
3. How to use NexoBrid
4. Possible adverse effects
5. How to store NexoBrid
6. Contents of the pack and other information

1. What NexoBrid is and what it is used for

What NexoBrid is

NexoBrid contains a mixture of enzymes called "enzymatically active bromelain concentrate", derived from an extract of the stem of the pineapple plant.

What NexoBrid is used for

NexoBrid is used to remove burned tissue from deep or partially deep skin burns in adults, adolescents, and children of all ages.

The use of NexoBrid may reduce the need for or extent of surgical removal of burned tissue and/or skin grafting.

2. What you need to know before using NexoBrid

Do not use NexoBrid:

• if you or your child are allergic to bromelain;
• if you or your child are allergic to pineapple;
• if you or your child are allergic to papaya/papain;
• if you or your child are allergic to any of the other components of the powder or gel (listed in section 6).

Warnings and precautions

Talk to your doctor or nurse before starting to use NexoBrid if:

• you or your child have heart disease;
• you or your child have diabetes;
• you or your child have an active peptic ulcer in the stomach;
• you or your child have vascular disease (with vascular occlusion);
• you or your child have enlarged veins near the burn area;
• you or your child have implants, pacemakers, or vascular shunts;
• you or your child have bleeding disorders or are taking anticoagulant medications;
• your wound(s) or your child's wound(s) have been exposed to chemicals and other hazardous substances;
• you or your child have lung disease;
• you or your child have or may have lung damage due to smoke inhalation;
• you or your child are allergic to latex, bee stings, or olive pollen. In this case, you or your child may also experience allergic reactions to NexoBrid.

Allergic reactions may cause, for example, breathing difficulties, skin swelling, hives, other skin reactions, skin redness, low blood pressure, increased heart rate, abdominal discomfort, or a combination of these effects. If you or your child notice any of these signs or symptoms, inform your doctor or caregiver immediately.

Allergic reactions can be severe and may require medical treatment.

In case of contact with the skin, remove NexoBrid by rinsing thoroughly with water. This is intended to reduce the likelihood of an allergic reaction to NexoBrid.

The use of NexoBrid to remove burned tissue may cause fever, wound inflammation or infection, or possibly systemic infection. You or your child may be monitored periodically for these potential problems, and you may receive medications to prevent or treat infections.

NexoBrid may reduce the blood's ability to clot, increasing the risk of bleeding. NexoBrid should be used with caution if you or your child are taking medications that reduce blood clotting (called anticoagulants) or if you or your child have a general tendency to bleed, a stomach ulcer, blood poisoning, or another condition that could cause bleeding. After treatment with NexoBrid, your doctor may check your blood clotting levels.

Direct contact of NexoBrid with the eyes should be avoided. If NexoBrid gets into the eyes, rinse them with plenty of water for at least 15 minutes.

To prevent wound healing problems, the treated burn will be covered as soon as possible with dressings or temporary or permanent skin substitutes.

NexoBrid must not be used for chemical burns, electrical burns, foot burns in patients with diabetes or occlusive arterial disease, contaminated burns, or burns where it could come into contact with foreign materials (e.g., implants, pacemakers, shunts) or large blood vessels, eyes, or other vital body parts. NexoBrid should be used with caution in areas with varicose veins (twisted and enlarged veins) to prevent the risk of bleeding from them.

Use of NexoBrid with other medicines

Tell your doctor if you or your child are using, have recently used, or might need to use any other medicines.

Your doctor will exercise caution and monitor for signs of reduced blood clotting or bleeding when prescribing other medicines that affect blood coagulation, as NexoBrid may reduce clotting.

NexoBrid may:

• increase the effects of certain medicines inactivated by liver enzymes called CYP2C8 and CYP2C9. This is because NexoBrid may be absorbed from the burn wound into the bloodstream. Some examples of such medicines are:

• amiodarone (used to treat certain types of irregular heartbeat),

• amodiaquine and chloroquine (used to treat malaria and certain inflammatory conditions),

• fluvastatin (used to treat high cholesterol),

• pioglitazone, repaglinide, tolbutamide, and glipizide (used to treat diabetes),

• paclitaxel (used to treat cancer),

• torasemide (used to increase urine flow),

• ibuprofen (used to treat fever, pain, and certain inflammatory conditions),

• losartan (used to treat high blood pressure (hypertension)),

• celecoxib (used to treat certain inflammatory conditions),

• warfarin (used to reduce blood clotting),

• phenytoin (used to treat epilepsy).

• intensify your or your child's reaction to the anticancer drugs fluorouracil and vincristine.

• cause an unwanted drop in blood pressure when you or your child are treated with medicines called ACE inhibitors, used to treat high blood pressure (hypertension) and other conditions.

• increase drowsiness when used together with medicines that may cause drowsiness. These medicines include, for example, sleeping pills, so-called tranquilizers, certain painkillers, and antidepressants.

• Silver sulfadiazine or povidone-iodine applied to the wound site may reduce the effectiveness of the medicine.

If you have any doubts about whether you or your child are taking any of the medicines listed above, speak with your doctor before using NexoBrid.

Pregnancy and breastfeeding

The use of NexoBrid is not recommended during pregnancy.

As a precautionary measure, breastfeeding should not be resumed for at least 4 days after NexoBrid application.

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before this medicine is used.

3. How to use NexoBrid

The application of NexoBrid is performed only by specialists in burn clinics. It must be prepared immediately before use and applied by a physician or other healthcare professional.

Apply 5 g of NexoBrid powder mixed with 50 g of gel at a thickness of 1.5 to 3 millimeters per burned area covering 2.5% of the total body surface area in an adult patient.

It should be left in place for 4 hours, after which it should be removed. A subsequent second application is not recommended.

• NexoBrid must not be applied to more than 15% (one-eighth) of the total body surface area in adults and children/adolescents aged 4 to 18 years.
• This medicinal product must not be applied to more than 10% of the total body surface area in children aged 0 to 3 years.

Instructions for preparing NexoBrid gel are included at the end of this leaflet, in the section intended for medical or healthcare professionals.

Before application to a burn wound, NexoBrid powder is mixed to form a gel. The gel must be used within 15 minutes of mixing.

• NexoBrid should be applied to a clean, moist, blister-free wound area.

• Other medications (such as silver sulfadiazine or povidone-iodine) must be removed from the wound prior to NexoBrid application.

• Prior to NexoBrid application, a dressing impregnated with an antibacterial solution should be applied to the wound for 2 hours.

• You or your child will be given an appropriate medication to prevent and treat pain, administered at least 15 minutes before NexoBrid application and before its removal.

• After removal of NexoBrid and the dead tissue from the wound, a dressing impregnated with an antibacterial solution will be applied for an additional 2 hours.

• The vial containing the powder, the gel container, and the prepared gel are for single use only.

If you use too much NexoBrid

If too much NexoBrid gel is applied to a burn, the excess gel should be wiped away.

If you have any further questions about the use of this medicine, ask your doctor.

4. Possible adverse effects

Like all medicines, NexoBrid can cause adverse effects, although not everyone experiences them.

Allergic reactions to NexoBrid may occur, which can cause, for example, breathing difficulties, skin swelling, hives, skin redness, low blood pressure, increased heart rate, and dizziness/vomiting/stomach cramps, or a combination of these effects. If you or your child experience any of these symptoms or signs, inform your doctor or caregiver immediately.

Very common (may affect more than 1 in 10 people)

• Fever

Common (may affect up to 1 in 10 people)

• Pain in the treated burn area (even when medications are used to prevent or reduce pain associated with the removal of burned tissue)
• Burn infection, including skin infection around the wound (cellulitis)
• Wound complications, including wound deepening, wound opening, wound drying or dehiscence, failure of skin grafts to heal properly
• Rash or redness in the area around the burn
• Non-severe allergic reactions such as rash
• Fast heartbeat
• Itching in the burned area, which is very common as part of the normal burn healing process

Uncommon

• Bruising at the wound site

Frequency not known (frequency cannot be estimated from available data)

• Severe allergic reactions, including anaphylaxis

Reporting of adverse effects

If you or your child experience any type of adverse effect, consult your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of NexoBrid

Keep this medicine out of the sight and reach of children.

Do not use NexoBrid after the expiry date stated on the label of the vial, bottle, and carton following “EXP/CAD”. The expiry date refers to the last day of the month indicated.

Store and transport refrigerated (between 2°C and 8°C).

NexoBrid must be stored in an upright position to keep the gel at the bottom of the bottle and in its original packaging to protect it from light.

Do not freeze.

NexoBrid must be used within a maximum of 15 minutes after mixing the powder with the gel.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of NexoBrid

• The active substance (in the powder of the vial) is a concentrate of proteolytic enzymes enriched in bromelain: one vial contains 5 g, corresponding to 0.09 g/g of concentrate of proteolytic enzymes enriched in bromelain after mixing.

• The other components are:

• for the powder: ammonium sulfate and acetic acid

• for the gel: carbomer 980, anhydrous disodium phosphate, sodium hydroxide, and water for injections.

Nature of the product and contents of the container

NexoBrid is supplied as a powder and gel for gel (powder in a vial [5 g] and gel in a bottle [50 g]), pack size of 1 (one pack contains one vial of powder and one bottle of gel).

The powder ranges from off-white to light cinnamon in colour and the gel is clear and colourless.

Further information about this medicine may be requested by contacting the marketing authorization holder.

Marketing Authorization Holder

MediWound Germany GmbH
Hans-Sachs-Strasse 100
65428 Rüsselsheim
Germany
e-mail: [email protected]

Manufacturer

Diapharm GmbH & Co. KG
Am Mittelhafen 56
48155 Münster
Germany

Date of the most recent revision of this leaflet:

Other sources of information>

Detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu. Links to other websites on rare diseases and orphan medicinal products are also available.

This information is intended for healthcare professionals only:

Preparation and administration

From a microbiological standpoint and given that the enzymatic activity of the product progressively decreases after mixing, the reconstituted product should be used immediately after preparation (within a maximum of 15 minutes).

NexoBrid must be applied to a moist, clean, and non-keratinized lesion area (after removal of blisters).

Topical medications (such as silver sulfadiazine or povidone-iodine) must be removed from the lesion area, and the wound should be cleaned before application of NexoBrid.

Preparation of the patient and the lesion area

• A total lesion area greater than 15% of the TBSA must not be treated with NexoBrid in adults and children/adolescents >3 years of age; in children aged 0 to 3 years, no more than 10% of the TBSA may be treated.
• Enzymatic debridement is a painful procedure and requires adequate analgesia or anesthesia. Pain management should be administered according to standard practices for large dressing changes; this should be initiated at least 15 minutes before application of NexoBrid.
• The wound should be thoroughly cleaned and the superficial keratin layer or blisters from the lesion area should be removed, as keratin will isolate the eschar from direct contact with NexoBrid and prevent its removal.
• An antibacterial-impregnated dressing should be applied for 2 hours.
• All topical antibacterial medications must be removed before application of NexoBrid. Residual antibacterial agents may reduce the activity of NexoBrid, thereby decreasing its efficacy.
• The area from which eschar removal is desired should be surrounded with an adhesive barrier made of sterile paraffin ointment applied several centimeters outside the treatment area (using a dispenser). The paraffin layer must not come into contact with the area to be treated to avoid covering the eschar, which would isolate it from direct contact with NexoBrid.

To prevent possible irritation of abraded skin from accidental contact with NexoBrid and possible wound bleeding, acute injured areas such as lacerations or escharotomy incisions should be protected with a layer of sterile greasy ointment or a greasy dressing (e.g., vaseline gauze). This medicine should be used with caution in areas with varicose veins to avoid erosion of the venous wall and the risk of bleeding.

• A sterile isotonic solution of 9 mg/ml (0.9%) sodium chloride should be sprayed onto the burn. The wound must remain moist during the application procedure.

Preparation of NexoBrid gel (mixing powder with gel)

• NexoBrid powder and gel are sterile. Aseptic technique must be used when mixing NexoBrid powder with the gel. The powder must not be inhaled. Use of gloves and protective equipment, as well as protective goggles and surgical mask, is required.

• The NexoBrid powder vial should be opened by carefully peeling off the aluminum closure cap and removing the rubber stopper.

• When opening the gel bottle, confirm that the tamper-evident ring is separating from the closure cap of the bottle. If the tamper-evident ring was already separated from the closure cap before opening, the gel bottle must be discarded and a new gel bottle used.

• NexoBrid powder is then transferred to the corresponding gel bottle.

• NexoBrid powder and gel must be thoroughly mixed until a uniform mixture of light cinnamon to light brown color is obtained. This usually requires mixing NexoBrid powder and gel for 1 to 2 minutes.

• NexoBrid gel should be prepared at the patient's bedside.

Application of NexoBrid

• Moisten the area to be treated by spraying sterile saline solution onto the area surrounded by the adhesive barrier of greasy ointment.
• NexoBrid must be applied topically to the burn within a maximum of 15 minutes after mixing, with a thickness of 1.5 to 3 millimeters.
• The burn should then be covered with a sterile occlusive film dressing that adheres to the sterile adhesive barrier material applied as per previous instructions (see Preparation of the patient and the lesion area). The NexoBrid gel should completely fill the occlusive dressing, and care must be taken not to leave air under the occlusive dressing. Applying gentle pressure over the contact area between the occlusive dressing and the adhesive barrier ensures adherence between the occlusive film and the barrier, as well as complete confinement of NexoBrid within the treatment area.
• The prepared wound should then be covered with a thick, loose, and soft dressing secured with a bandage.
• The dressing should remain on the wound for 4 hours.

Removal of NexoBrid

• Removal of NexoBrid is a painful procedure and requires adequate analgesia or anesthesia. Appropriate preventive analgesic medications should be administered at least 15 minutes before the application of NexoBrid.
• After 4 hours of treatment with NexoBrid, the occlusive dressing should be removed using aseptic techniques.
• The adhesive barrier should be removed using a sterile blunt-edged instrument (e.g., a tongue depressor).
• The dissolved eschar should be removed from the wound using a sterile blunt-edged instrument.
• The wound should be thoroughly cleaned first with a large sterile dry gauze or towel, and then with a sterile gauze or towel impregnated with sterile isotonic solution of 9 mg/ml (0.9%) sodium chloride. The treated area should be rubbed until a pink surface with hemorrhagic spots or whitish tissue appears. This rubbing maneuver will not remove adherent, undissolved eschar from areas where it persists.
• An antibacterial-impregnated dressing should be applied for an additional 2 hours.

Wound care after debridement

• The debrided area should be immediately covered with temporary or permanent wound dressings or skin substitutes to prevent desiccation and/or formation of pseudoeschar and/or infections.
• Before applying a permanent skin cover or temporary skin substitute to a recently debrided area using enzymatic methods, a moist-to-dry dressing should be applied.
• Prior to application of grafts or primary dressings, the debrided wound bed should be cleaned and refreshed by, for example, brushing or scraping to allow adherence of the dressings.
• In full-thickness wounds and deep burns, autografts should be implanted as soon as possible after debridement with NexoBrid. The implantation of permanent skin covers (e.g., autografts) should also be carefully evaluated shortly after debridement with NexoBrid in deep partial-thickness wounds.

Safety handling recommendations

Each vial, gel, or reconstituted gel of NexoBrid must be used for a single patient only.

There have been reports of occupational exposure to bromelain leading to sensitization. Sensitization may have occurred due to inhalation of bromelain powder. Allergic reactions to bromelain include anaphylactic reactions and other immediate-type reactions with manifestations such as bronchospasm, angioedema, urticaria, and mucosal and gastrointestinal reactions. When mixing NexoBrid powder with the gel, appropriate handling is required, including the use of gloves and protective equipment, as well as protective goggles and surgical mask. The powder must not be inhaled.

Avoid accidental ocular exposure. In case of ocular exposure, irrigate the exposed eyes with abundant water for at least 15 minutes. In case of cutaneous exposure, remove NexoBrid by rinsing with water.

Disposal

Disposal of unused medicine and of all materials that have come into contact with it must be carried out in accordance with local regulations.